The goal of this project is to study the feasibility of nutritional and pharmacological intervention to promote the activity of established and potential cancer chemotherapeutic agents, and to increase their selectivity for tumor cells. Approaches to this goal include the following: 1) alteration of the nutritional status of tumor cells, both in culture or in vivo, to produce conditions interfering with the metabolic inactivation of the chemotherapeutic agent. This approach will be particularly directed against resistant cell lines; 2) modification of the cell membrane of susceptible and resistant varieties of tumor cells by the use of either available or newly synthesized membrane-reactive agents; 3) synthesis of analogs of known agents in order to introduce modifications to make them more suitable for the regimens described above.